TESTS OF THE DOUBLE-STRAND BREAK, LETHAL POTENTIALLY LETHAL AND REPAIR-MISREPAIR MODELS FOR MAMMALIAN-CELL SURVIVAL USING DATA FOR SURVIVALAS A FUNCTION OF DELAYED-PLATING INTERVAL FOR LOG-PHASE CHINESE-HAMSTER V79 CELLS
Cs. Lange et al., TESTS OF THE DOUBLE-STRAND BREAK, LETHAL POTENTIALLY LETHAL AND REPAIR-MISREPAIR MODELS FOR MAMMALIAN-CELL SURVIVAL USING DATA FOR SURVIVALAS A FUNCTION OF DELAYED-PLATING INTERVAL FOR LOG-PHASE CHINESE-HAMSTER V79 CELLS, Radiation research, 148(3), 1997, pp. 285-292
Our data (Reddy et al., Raniat. Res. 141, 252-258, 1995) on the kineti
cs of the repair of potentially lethal damage in log-phase Chinese ham
ster V79 cells are used to test some predictions which arise from the
different assumptions of the repair-misrepair (RMR) (C. A. Tobias, Rad
iat. Res. 104, S77-S95, 1985), lethal-potentially lethal (LPL) (S. B.
Curtis, Radiat. Res. 106, 252-270, 1986) and double-strand break (DSB)
(J. Y. Ostashevsky, Radiat. Res. 118, 437-466, 1989) models. The LPL
model defines the time available for repair of PLD (t(rep)) as the tim
e taken to reach maximal survival in a delayed-plating recovery experi
ment. Those data show that after this time has elapsed, contrary to th
e expectation of the LPL model, survival can be increased by changing
the medium used for delayed plating from fresh growth medium to condit
ioned medium. According to the RMR model, all potentially lethal lesio
ns should also be committed by that time and be unavailable for repair
in the new medium. Only the DSB model correctly predicted that PLD (=
DSBs) would still be available for repair after that time. Second, da
ta for split-dose recovery are used to predict the first-order kinetic
s time constant for DSB repair (tau(DSBR)) using the DSB model (24 +/-
1.5 min). This value is nearly identical to the value of 27 +/- 1 min
determined from the data obtained by Cheong et al. using pulsed-field
gel electrophoresis (PFGE) (Mutat. Res. 274, 111-122, 1992). The valu
e based on PFGE is used to calculate the value of t(rep) predicted by
the DSB model (2.6 +/- 0.1 h), which agrees with the value determined
experimentally as the time when changing the delayed-plating medium fr
om growth medium to conditioned medium no longer gives the full recove
ry seen with delayed plating in conditioned medium (2.5 h). However, s
ome recovery was seen for a change in the medium (growth medium to con
ditioned medium) up to 5-6 h postirradiation. Reanalysis of the origin
al data on DSB repair shows that they are consistent with two first-or
der repair rates (18 +/- 7 min and about 52 min). These results are co
nsistent with two pools of DSBs (or cells), each with their own t(rep)
. The early t(rep), associated with tau(fast), is predicted to be 1.7
+/- 0.7 h, and the late t(rep), associated with tau(slow), is predicte
d to be about 5 h. Both values are in excellent agreement with the tim
es at which changing from growth medium to conditioned medium no longe
r gives the full recovery seen in conditioned medium only (the early t
(rep)), and the time when changing from growth medium to conditioned m
edium produces no further increase in survival (the late t(rep)), resp
ectively. It is noted that attempts to correlate radiosensitivity with
the rates of DSB repair, rather than using an explicit model such as
the DSB model, are unlikely to be productive since survival depends on
both tau(DSBR) and t(rep) (as defined in the DSB model) and the latte
r may be the more important determinant of radiosensitivity (as it app
ears to be for ataxia telangiectasia cells compared to normal fibrobla
sts and for irs compared to V79 cells). (C) 1997 by Radiation Research
Society.